In vitro and in vivo characteristics of connexin 43-modified human skeletal myoblasts as candidates for prospective stem cell therapy for the failing heart

Kolanowski, Tomasz; Rozwadowska, Natalia; Malcher, Agnieszka; Szymczyk, Ewa; Kasprzak, Jarosław D.; Mietkiewski, Tomasz; Kurpisz, Maciej

doi:10.1016/j.ijcard.2014.02.009

Cited by 19 publications

(34 citation statements)

References 34 publications

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“…Animal studies have demonstrated that the transplantation of autologous SM ameliorated the mechanical function and electrical activity of the animal heart after experimentally induced myocardium infarction [29,30]. In many instances, however, transplanting SM to injured heart area is not enough for repair the cardiac lesion, since angiogenesis also plays an important role in myocardial regeneration [31].…”

Section: Discussionmentioning

confidence: 99%

Cardiac Analysis of Autologous Transplantation of Cocultured Skeletal Myoblasts and Mesenchymal Cells in a Rat Model Doxorubicin-Induced Cardiotoxicity: Histopathological and Functional Studies

Dias¹,

Francisco²,

Cardoso³

2015

J Clin Exp Cardiolog

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Objective: Investigate the functional and histopathological effects of combined transplantation of mesenchymal stem cells (MSCs) and skeletal myoblasts (SM) in rats submitted to doxorubicin (DOX) induced cardiomyopathy. Methods:Myocardiopathy was induced through intraperitoneal applications of 3.75 mg/kg/day DOX once a week for 4 weeks in all experimental animals. Echocardiography examination was conducted to evaluate heart function. Myocardial cell apoptosis was examined morphologically by optical microscopy. The expression of both, von Willebrand factor and MyoD proteins was analysed using immunohistochemical staining. Results:Our results showed that all the experimental animals developed cardio-toxicity and exhibited decrease in heart function 4 weeks after the administration of DOX (P<0.05). The ventricular function significantly improved in rats that received sub-epicardial injection of co-culture of SM and MSC (CO group) when compared to rats that received only saline sub-epicardial injection (CG group) (P<0.05). Conclusion:The results of this study provide evidences that the myocardial co-culture transplantation of SM and MSCs contributed to the treatment the DOX-induced cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

Cardiac Analysis of Autologous Transplantation of Cocultured Skeletal Myoblasts and Mesenchymal Cells in a Rat Model Doxorubicin-Induced Cardiotoxicity: Histopathological and Functional Studies

Dias¹,

Francisco²,

Cardoso³

2015

J Clin Exp Cardiolog

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“…The advantages and limitations of each stem cell with regard to the possible emergence of ethical concerns (symbolized by ¥), the invasiveness and collection (from + to ++++), the isolation procedure, the abundance (from + to ++++), expansion and proliferation rate, the transdifferentiation capacity, the paracrine effects or/and cardiomyogenic potential, the survival and engraftment capacity as well as the immunogenic, oncogenic or teratogenic risks is given in the accessory side tables. The left table abridges bone marrow-derived stem cells [3,[19][20][21]27,28], cortical bone-derived stem cells [32,33], adipose tissue-derived stem cells [34,37,39,41] and gestation-related stem cells [42][43][44][45][46][47][48][49]51,54] and the right table abridges cardiac stem cells [57,59,60], skeletal muscle stem cells [62,63,66] and induced pluripotent stem cells [67,[69][70][71]. The human body scheme was constructed with images sourced from Servier Medical Art (http://www.servier.com/ Powerpoint-image-bank) and Cientic website (http://www.cientic.com/).…”

Section: Adipose Tissue-derived Stem Cellsmentioning

confidence: 99%

“…In addition, resistance to low oxygen tension conditions have been reported (Fig. 1) [12,62,63]. However, stem cells collected from skeletal muscle are unipotent and, once transplanted, may induce arrhythmias owing to the lack of expression of gap junction proteins, which are crucial for cell-cell electric coupling [62][63][64].…”

Section: Skeletal Muscle Stem Cellsmentioning

confidence: 99%

“…1) [12,62,63]. However, stem cells collected from skeletal muscle are unipotent and, once transplanted, may induce arrhythmias owing to the lack of expression of gap junction proteins, which are crucial for cell-cell electric coupling [62][63][64]. Similarly to the aforementioned stem cells, SkMSC main activity is through the release of paracrine cues, such as hepatocyte growth factor (HGF), VEGF and stromal cellderived factor 1 (SDF-1), which exert pro-angiogenic, anti-fibrotic and anti-apoptotic activities [65,66].…”

Section: Skeletal Muscle Stem Cellsmentioning

confidence: 99%

“…The majority of the investigations sought to enhance the expression of a certain gene [23,24,61,63,66,74,76,102,104,109,110,117] or to transfect cells with microRNAs (miRs) [16,19]. The only example of gene repression was reported by Wang et al [39], who described the silencing of prolyl hydroxylase domain protein 2 gene (PHD2) as an alternative combined genetic and cell therapy approach.…”

Section: Genetic Engineeringmentioning

confidence: 99%

See 2 more Smart Citations

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

Trindade

Leite‐Moreira

Ferreira-Martins

et al. 2017

International Journal of Cardiology

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Today there is an increasing demand for heart transplantations for patients diagnosed with heart failure. Though, shortage of donors as well as the large number of ineligible patients hurdle such treatment option. This, in addition to the considerable number of transplant rejections, has driven the clinical research towards the field of regenerative medicine. Nonetheless, to date, several stem cell therapies tested in animal models fall by the wayside and when they meet the criteria to clinical trials, subjects often exhibit modest improvements. A main issue slowing down the admission of such therapies in the domain of human trials is the lack of protocol standardization between research groups, which hampers comparison between different approaches as well as the lack of thought regarding the clinical translation. In this sense, given the large amount of reports on stem cell therapy studies in animal models reported in the last 3 years, we sought to evaluate their advantages and limitations towards the clinical setting and provide some suggestions for the forthcoming investigations. We expect, with this review, to start a new paradigm on regenerative medicine, by evoking the debate on how to plan novel stem cell therapy studies with animal models in order to achieve more consistent scientific production and accelerate the admission of stem cell therapies in the clinical setting.

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Safety, feasibility and effectiveness of first in‐human administration of muscle‐derived stem/progenitor cells modified with connexin‐43 gene for treatment of advanced chronic heart failure

Gwizdała

Rozwadowska

Kolanowski

et al. 2017

European J of Heart Fail

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Aims To assess the safety and efficacy of transendocardial delivery of muscle‐derived stem/progenitor cells with connexin‐43 overexpression (Cx‐43‐MDS/PC) in advanced heart failure (HF). Methods and results Thirteen subjects with advanced HF, New York Heart Association (NYHA) class II–III were enrolled and treated with targeted injection of Cx‐43‐MDS/PCs and then monitored for at least 6 months. Overexpression of Cx43 (Cx43+) was significantly higher in all but one subject (Cx43–). Injection of MDS/PCs was associated with significant improvement of exercise capacity: NYHA (3 ± 0 vs. 1.8 ± 0.7, P = 0.003), exercise duration (388.69 ± 141.83 s vs. 462.08 ± 176.69 s, P = 0.025), peak oxygen consumption (14.38 ± 3.97 vs. 15.83 ± 3.74 ml/kg.min, P = 0.022) and oxygen pulse (10.58 ± 2.89 vs. 18.88 ± 22.63 mLO2/heart rate, P = 0.012). Levels of BNP, left ventricular (LV) ejection fraction and LV end‐diastolic volumes tended to improve. There was a significant improvement of the mean unipolar voltage amplitudes measured for the injected segments and the entire left ventricle (9.62 ± 2.64 vs. 11.62 ± 3.50 mV, P = 0.014 and 8.83 ± 2.80 vs. 10.22 ± 3.41 mV, P = 0.041, respectively). No deaths were documented, Cx43+ (n = 12) subjects presented no significant ventricular arrhythmia; one Cx43– subject suffered from ventricular tachycardia (successfully treated with amiodarone). Conclusions Injection of Cx‐43‐MDS/PCs in patients with severe HF led to significant improvement in exercise capacity and myocardial viability of the injected segments while inducing no significant ventricular arrhythmia. This may arise from improved electrical coupling of the injected cells and injured myocardium and thus better in‐situ mechanical cooperation of both cell types. Therefore, further clinical studies with Cx43+ MDS/PCs are warranted.

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In vitro and in vivo characteristics of connexin 43-modified human skeletal myoblasts as candidates for prospective stem cell therapy for the failing heart

Cited by 19 publications

References 34 publications

Cardiac Analysis of Autologous Transplantation of Cocultured Skeletal Myoblasts and Mesenchymal Cells in a Rat Model Doxorubicin-Induced Cardiotoxicity: Histopathological and Functional Studies

Cardiac Analysis of Autologous Transplantation of Cocultured Skeletal Myoblasts and Mesenchymal Cells in a Rat Model Doxorubicin-Induced Cardiotoxicity: Histopathological and Functional Studies

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

Safety, feasibility and effectiveness of first in‐human administration of muscle‐derived stem/progenitor cells modified with connexin‐43 gene for treatment of advanced chronic heart failure

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